Objective Non-Hodgkin lymphoma (NHL) arising as a secondary malignancy in patients treated for classical Hodgkin lymphoma (cHL) is an infrequent and challenging clinical scenario. NHL can be presented synchronously with cHL or may develop later, sequentially, up to years after treatment for cHL. The relationship between the two lymphomas is unclear, and there are no clear guidelines for the management of these patients. We would like to find a better clinical understanding of this issue so this study investigates the occurrence and clinical characteristics of secondary NHL. Materials and methods In this retrospective cohort examination, we collected cHL cases when NHL occurred during or after the course of treating cHL. We performed the histopathologic revisions of the samples, and in every case where the quality of the sample was lower, we performed molecular examinations to find the association between cHL and NHL. We performed next-generation genome sequencing (NGS) and immunoglobulin heavy-chain variable region gene (IgHV) clonality testing. Results In a cohort of 164 cHL patients diagnosed between 2011 and 2020, six patients were identified with NHL during rebiopsy prompted by lymphoma relapse or progression. Among these, five patients were diagnosed with post-germinal center-originated diffuse large B-cell lymphoma (post-GC DLBCL), and one patient presented high-grade B-cell lymphoma (HG-BCL). The NHL manifestation differed in its timing: three cases emerged after successful cHL treatment, with at least 18 months of complete remission, while the other three patients faced primary refractory cHL. Notably, the primary refractory cases did not exhibit a confirmed clonal relationship between cHL and NHL, but NGS data raised the possibility of synchronous NHL in one case. In contrast, among the patients with sequentially occurring NHL, polymerase chain reaction (PCR) testing of the IgHV gene affirmed a clonal connection between cHL and secondary DLBCL in one case, while the high morphological similarity suggested a potential clonality between the two lymphomas in another case. Conclusion This study reveals that secondary NHL may manifest both synchronously and sequentially following cHL. Our results suggest that synchronous NHL has a worse prognosis compared to sequential cases when the different lymphomas are not recognized at the time of diagnosis. As our data showed, in some cases, mutations that accompany the tumor cells throughout their clonal evolution can be identified, with additional mutations later on. In the future, next-generation sequencing (NGS)-based processing of liquid biopsy samples can overcome the limitations resulting from the spatial heterogeneity of lymphoid malignancies. Over the long term, this identification could lead to early patient selection and alternative treatment strategies, ultimately leading to improved prospects for cure.

UNASSIGNED: Multiple Primary Malignant Neoplasms (MPMNs) are rare and refer to the occurrence of two or more distinct primary cancers with unrelated histopathological features in one patient. MPMNs can be classified as synchronous when tumors appear simultaneously or within six months of each other, and as metachronous when identified six months or more after the initial cancer diagnosis. While breast cancer often co-occurs with other primary cancers such as colorectal, endometrial, and ovarian cancers, the simultaneous presence of invasive lobular breast carcinoma and clear cell renal cancer is rare.
METHODS: Here, we present the case of a 59-year-old postmenopausal woman who initially presented with breast carcinoma. Further investigation revealed a mass in the left kidney. The patient underwent a radical mastectomy and axillary dissection, followed by a left nephrectomy. After 8 months follow up, the patient is doing well and disease-free.
UNASSIGNED: Based on our case and literature review, the co-occurrence of breast carcinoma with renal cell carcinoma (RCC) is uncommon. Most reported cases involve metastatic tumors or metachronous breast malignancy with RCC. The etiology of synchronous malignancy is complex, and treatment options usually include a combination of surgery and/or adjuvant therapy.
CONCLUSIONS: This case report contributes valuable insights to the limited literature on synchronous breast cancer with renal cell carcinoma. The rarity of this simultaneous occurrence underscores the importance of considering such cases. Documenting these cases is crucial for increasing awareness and reducing the resulting morbidity and mortality.

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Synchronous pancreatic neuroendocrine tumors and renal cell cancer are extremely rare. Von-Hipple-Landau syndrome is a major association. A 43-year-old male patient with left upper quadrant pain and significant weight loss was diagnosed with a synchronous pancreatic tail neuroendocrine tumor with solitary splenic metastasis and a clear-cell renal cell carcinoma of the left kidney. Sonography and a computed tomography scan of the abdomen showed a complex exophytic left renal mass and a necrotic lesion limited to the spleen. Although not apparent on preoperative imaging, distal pancreatic mass was also discovered intraoperatively. Subsequently, left radical nephrectomy, splenectomy, and distal pancreatectomy were performed, and the synchronous primaries and splenic metastasis were confirmed histopathologically. This case is unique in that it demonstrates multiple extremely rare events occurring simultaneously, namely pancreatic and kidney primaries, as well as solitary splenic metastasis.

UNASSIGNED: Mutations of CHEK2 are usually inherited and have been implicated in breast cancers, colorectal cancers, thyroid cancers, kidney cancers, and prostate cancers. The CHEK2 gene codes for checkpoint kinase 2 protein which is an effector in the ATM-CHEK2-p53 pathway and responds to DNA double-strand breaks.
UNASSIGNED: We describe a unique case of a 29-year-old Canadian female who presented with synchronous papillary thyroid carcinoma and rectal adenocarcinoma who was subsequently found to have a sporadic CHEK2 (checkpoint kinase 2) mutation. She presented with an 8-month history of bright red blood per rectum and saw two different physicians who diagnosed hemorrhoids and possible rectal ulcers, respectively. When the symptoms continued, the patient pursued a colonoscopy exam which found a large rectal tumor. Subsequent clinical staging diagnosed a rectal adenocarcinoma and a synchronous papillary thyroid carcinoma. Due to her synchronous tumors, a genetic panel was performed, which revealed a low-risk CHEK2 mutation. Our patient had a full response to neoadjuvant brachytherapy of the rectum and surgical treatment of her cancers.
UNASSIGNED: This is the first case report, to our knowledge, of a patient with a CHEK2 mutation who presented with synchronous papillary thyroid carcinoma and invasive colonic adenocarcinoma. The incidence of colorectal cancers and papillary thyroid cancers in those under 30 with no family history is very low, which signifies the rarity of their simultaneous occurrence at such a young age.

Lynch syndrome-associated endometrial cancer patients often present multiple synchronous tumors and this assessment can affect treatment strategies. We present a case of a 27-year-old woman with tumors in the uterine corpus, cervix, and ovaries who was diagnosed with endometrial cancer and exhibited cervical invasion and ovarian metastasis. Her family history suggested Lynch syndrome, and genetic testing identified a variant of uncertain significance, MLH1 p.L582H. We conducted immunohistochemical staining, microsatellite instability analysis, and Sanger sequencing for Lynch syndrome-associated cancers in three generations of the family and identified consistent MLH1 loss. Whole-exome sequencing for the corpus, cervical, and ovarian tumors of the proband identified a copy-neutral loss of heterozygosity (LOH) occurring at the MLH1 position in all tumors. This indicated that the germline variant and the copy-neutral LOH led to biallelic loss of MLH1 and was the cause of cancer initiation. All tumors shared a portion of somatic mutations with high mutant allele frequencies, suggesting a common clonal origin. There were no mutations shared only between the cervix and ovary samples. The profiles of mutant allele frequencies shared between the corpus and cervix or ovary indicated that two different subclones originating from the corpus independently metastasized to the cervix or ovary. Additionally, all tumors presented unique mutations in endometrial cancer-associated genes such as ARID1A and PIK3CA. In conclusion, we demonstrated clonal origin and genomic diversity in a Lynch syndrome-associated endometrial cancer, suggesting the importance of evaluating multiple sites in Lynch syndrome patients with synchronous tumors.

UNASSIGNED: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems. Patients with SLE are prone to a variety of malignancies, especially neoplasms of the female reproductive tract. Synchronous tumors, considered to involve multiple sites, are rare in the female reproductive tract. There are hardly any reports of SLE with synchronous reproductive tract tumors.
UNASSIGNED: We report the occurrence of two to three reproductive tract tumors in two women with SLE. A 52-year-old woman was diagnosed with vulvar cancer and cervical cancer. Another woman, aged 67, was diagnosed with concurrent vulvar cancer, vaginal cancer, and cervical cancer and also presented with a suspected lung cancer.
UNASSIGNED: The presence of synchronous tumors of the reproductive tract in patients with SLE is uncommon and can be easily disregarded. It is crucial to highlight that SLE patients with multiple primary malignancies exhibit notable late-stage presentation at the time of diagnosis, inadequate disease-free survival, poor overall survival, rapid progression rates, and mortality. Consequently, greater awareness must be raised regarding synchronous reproductive tract tumors in patients with SLE. Regular comprehensive cancer screening and management should be implemented for individuals diagnosed with SLE.

Over the past decade, a series of rare and extraordinary uterine tumors have been discovered, with some featuring exceptionally uncommon tumor types. This highlights the growing recognition of these rare tumors due to evolutionary radiologic advancements. However, evaluating these patients requires adequate understanding to avoid misinterpretation and potential confusion with alternative differential diagnoses. This case is the first documented instance of two coexistent uterine benign tumors in a 45-year-old unmarried female patient. The patient\'s medical, gynecological, and surgical histories were unremarkable. Conventional abdominopelvic imaging via computed tomography (CT) and magnetic resonance imaging (MRI) revealed significant uterine expansion, indicating an atypical leiomyomatous or potentially leiomyosarcomatous mass. Subsequently, [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET)/CT revealed hypermetabolic uterine enlargement, suggesting further evaluation. The patient underwent radical hysterectomy, and histopathological analysis revealed multiple uterine fibroids concurrently existing against the uterine angiomatosis. This case is the first documented instance of intricate pathological interplay within the uterus.

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In people with cancer, multiple primary malignant neoplasms (MPMNs) are not unusual, and they may be caused by risk factors such as genetics, viral infection, smoking, environmental factors, or treatment-related variables. The frequency of MPMNs occurring in the same or separate organ systems is between 2% and 17%. The 5-year breast cancer survivors have been found to have around 3.6% chance of acquiring another neoplasm. In this case report, we present a very rare simultaneous occurrence of two highly malignant tumors - triple-negative breast cancer and cutaneous melanoma. We performed genetic tests for determining the link between both neoplasms. The patient was treated in an adjuvant setting with chemotherapy and immunotherapy with pembrolizumab. According to epidemiological studies, for primary cutaneous melanoma following breast cancer, the standardized incidence ratio (SIR) varied from 1.03 to 4.10, while for primary breast carcinoma following cutaneous melanoma, it varied from 1.16 to 5.13. A number of risk factors have been proven to increase the risk of a second primary malignancy. This case highlights the importance of risk factor assessment and thorough primary workup of each patient. It emphasizes the need for a personalized approach when treating synchronous neoplasms.